It has been known for more than a decade that macromolecules can be taken up by mammalian cells. Only recently did it become apparent that this uptake can exert critical functions in host cells. Little work has been focused upon the physiology and control of macromolecular uptake, and upon the factors that influence the fate and expression of ingested macromolecules uptake, and upon the factors that influence the fate and expression of ingested macromolecules. Quantitative assays have been worked out to measure the net uptake and the intracellular breakdown of 125I-albumin in cultured cells. It was found that the basic polymers (basic polyamino acids, DEAE-dextran) markedly enhance albumin uptake. The mechanisms and the morphological correlates of this effect are under investigation. It was shown that different proteins are taken up at different rates, but the parameters that define selectivity have not so far been studied in a systematic fashion. The use of synthetic copolymers of known structure provides tools to clarify this problem. Proteins, once ingested, are subjected to intracellular digestion and must escape this process in order to express biological functions. The factors that influence this balance are also being investigated. They are of considerable interest to biologists concerned with antigen uptake, genetic transformation and genetic therapy, cancer chemotherapy and with protein-mediated uptake of biological substances.